History and Update of Chapters 797 and 800

Transcription

1 United States Pharmacopeia (USP) History and Update of Chapters 797 and 800 Lisa D. Ashworth, BS Pharm, RPh, FACA 50 th Annual C.E. Seminar Saturday, January 27, 2018, Dallas, Texas

2 Disclaimer The views and opinions expressed are those of the speaker and are not endorsed by or affiliated with USP. Conflict of Interest The speaker has no conflicts to disclose.

3 Objectives At the conclusion of this activity, the pharmacist participant will be able to: Understand the history of USP as a standard setting organization. Discuss the history and importance of USP 797 as the standard for compounding sterile preparations. Discuss the history and importance of USP 800 for handling hazardous medications in healthcare settings. Knowledge of differences between USP 797 and TSBP regulations. At the conclusion of this activity, the technician participant will be able to: Know the history of USP as a standard setting organization. Recognize the importance of USP 797 ands the standard for compounding sterile preparations. Recognize the importance of USP 800 as the standard for handling hazardous medications in healthcare settings.

4 USP s Beginning USP was founded in 1820 by 11 physicians, in Washington, D.C. 4

5 The first Pharmacopeia (1820) The first Pharmacopoeia of the United States contained 217 of the most fully established and best understood medicines in the U.S. It was published by the authority of the medical societies and colleges. 5

6 Legal Recognition in the US 1848 Drug Import Act recognized USP standards to stop the dumping of drugs by Europeans 1906 Pure Food and Drugs Act enforced USP and NF standards for strength, quality, and purity 1994 Dietary Supplement Health Education Act recognize USP standards for dietary supplements 1938 Food, Drug and Cosmetic Act recognized USP & NF standards for strength, quality, purity, packaging, and labeling 6

7 Legal Recognition in the US The requirements of the Federal Food Drug and Cosmetic Act (FD&C Act) apply equally to drugs that are compounded and those that are manufactured FDA Modernization Act Sec. 503A stated that compounding must comply with USP-NF standards and chapter on pharmacy compounding 2003 Medicare Modernization Act requested USP to develop and revise the Model Guidelines for Medicare Formularies 2010 Affordable Care Act recognizes USP Model Guidelines to assess coverage of Essential Health Benefits 2013 Drug Quality and Security Act recognize USP monographs for bulk drug substances and USP chapters on pharmacy compounding 7

8 Legal Recognition in the US 2013 Drug Quality and Security Act recognized USP monographs for bulk drug substances and USP chapters on pharmacy compounding As a result of the October 2012 compounding disaster Described 503A pharmacies Described 503B pharmacies Reinforced or continued things commissioned in FDAMA 1997 Pharmacy Compounding Advisory Committee (PCAC) Do Not Compound or Negative List Positive List Demonstrably Difficult to Compound List Does not apply to Animal Compounding Questions Dietary Supplements and Herbals used in compounding that have a USP monograph 8

9 USP Today Scientific non-profit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements USP s Mission: To improve global health through public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods. USP Headquarters Rockville, MD 9

10 USP The Organization What We Do Today Establish and disseminate public written standards for the quality, purity, identity, strength, and labeling of medicines Provide recommendations to practitioners on the safe use of medicines Work with international health agencies to improve the quality of medicines worldwide Educate practitioners, producers and others seeking information on quality and USP standards 10

11 USP Standards The United States Pharmacopeia National Formulary (USP NF) Food Chemicals Codex (FCC) USP Dietary Supplements Compendium (DSC) USP Compounding Compendium (CC) USP Medicines Compendium (MC) Herbal Medicines Compendium (HMC) Reference Standards Other Resources Pharmacopeial Forum (PF) FCC Forum (FCCF) USP Dictionary Chromatographic Columns 11

12 USP Compounding Compendium Launched November 3, 2014 Electronic Download includes: Mission & Preface General Notices & Requirements Compounding Related Chapters 6 essential compounding chapters Supporting General Chapters Over 40 referenced Chapters Compounded Preparation Monographs 175 formulations Downloadable pdf Annual Subscription

13 USP Standards - Setting Process EC Surveys Stakeholders for Needed Standards Comments considered Comments Incorporated, back to PF, or for Ballot EC/EP Researches Standard EC/USP Review Comments No EC Ballots Yes EC Writes Standard Propose Standard in PF for 90 days Standards in USP- NF Generally Become Official 6 months post publication 13

14 General Chapters Overview General Chapters can be: Enforceable Numbered below <1000> Informational Numbered above <1000> Specific for dietary supplements Numbered above <2000> Terminology Shall requirements Must Should recommendations 14

15 How often are USP Compounding Chapters revised? A. Ideally every 5 years B. USP Chapters are living standards constantly in revision C. Every 10 years D. All of the above 15

16 Official Compounding General Chapters <795> Pharmaceutical Compounding Nonsterile Preparations <797> Pharmaceutical Compounding-Sterile Preparations <800> Hazardous Drugs Handling in Healthcare Settings <1163> Quality Assurance in Pharmaceutical Compounding <1160> Pharmaceutical Calculations in Prescription Compounding <1176>Prescription Balances & Volumetric Apparatus Unofficial <1168> Compounding for Investigational Studies 16

17 Pharmaceutical Compounding Sterile Preparations General Chapter <797> 17

18 USP <797>: Revision History Sterile Compounding Standards 1992 First Standard proposed in PF18(2) Mar-April 1992 <1074> Dispensing Practices for Sterile Drug Products Intended for Home Use 1996 Revised in USP23-NF18 5th supplement <1206> Sterile Drug Products for Home Use General Chapter <797> History 2004 First Published in USP27-NF22 Revision from <1206> Sterile Drug Products for Home Use 2008 First Revised in USP 31-NF26 2S Official on June 1, Proposed Revision issued for comment September Intent to Revise Comments Due by January 31, to current EC begins review of ALL of the almost 9,000 comments received 2017 November 1, USP announced the chapter is anticipated to be published in the PF 44(5) September-October 2018 for a second round of public comment 18

19 USP <797>: Introduction Purpose: Provide minimum practice and quality standards for compounded sterile preparations (CSPs) based on current scientific information and best sterile compounding practices Objective: To describe conditions and practices to prevent harm, including death, to patients that could result from (1) microbial contamination (nonsterility) (2) excessive bacterial endotoxins Contaminants of concern include: Bacteria (3) variability in the intended strength of correct ingredients that exceeds either Fungus monograph limits for official articles or 10% for nonofficial articles Pyrogens (4) unintended chemical and physical contaminants Particulate matter (5) ingredients of inappropriate Allergens quality in compounded sterile preparations (CSPs) Drug residues 19

20 USP <797>: Major Elements Key Definitions CSP Risk Levels Facilities Monitoring 20

21 USP <797>: Key Definitions ISO Classification defines performance of environment with respect to total particulates per volume Class Name Particle Count ISO Class ISO, m , , , ,520,000 Primary Engineering Control (PEC) Source of ISO Class 5 environment where compounding occurs. 21

22 USP <797>: Key Definitions Buffer Area (or Cleanroom) ISO Class 7 area where the PEC is physical located. Used for preparation and staging of components and supplies to be used when compounding Ante-Area ISO Class 8 where personnel hand hygiene and garbing occurs. Serves as a transition area to maintain pressure relationships for air to flow from clean to dirty areas PEC 22

23 USP <797>: Key Definitions Critical Site Any component of fluid pathway surface or opening exposed to air, moisture, or touch Direct Compounding Area (DCA) Critical area within an ISO Class 5 PEC where critical sites are exposed to unidirectional first air Critical Site PEC DCA 23

24 USP <797>: CSP Microbial Contamination Risk Levels Low-Risk with 12 hour Low-Risk Level CSPs Medium- Risk Level CSPs High-Risk Level CSPs Controlled Room Temperature (20 to 25 C) 12 hours 48 hours 30 hours 24 hours Cold Temperature (2 to 8 C) 12 hours 14 days 9 days 3 days Solid Frozen State (- 25 to -10 C) N/A 45 days 45 days 45 days 24

25 USP <797>: Monitoring - Personnel Gloved Fingertip Testing Aseptic Media Fill Testing Surface Sampling 25

26 USP <797>: Monitoring Facilities Nonviable Particle Testing Air Viable Sampling Surface Sampling Pressure Differential 26

27 TSBP and USP 797 Differences TSBP states more specifics about training of Personnel in Sections (2) Pharmacists (3) Pharmacy technicians and pharmacy technician trainees Subsection B under both(2) & (3) states the completion of a single course and the # of hours of instruction (6) Environment (A) Low and Medium Risk Preparations (A) The clean room (A) (iv) shall be designed such that hand sanitizing and gowning occurs outside the buffer area but allows hands-free access by compounding personnel to the buffer area; (B) (xi) contain an ante-area that provides at least an ISO class 8 air quality and contains a sink with hot and cold running water that enables hands-free use with a closed system of soap dispensing to minimize the risk of extrinsic contamination. A Class B pharmacy may have a sink with hot and cold running water that enables hands-free use of a closed system of soap dispensing immediately outside the ante-area if antiseptic hand cleansing is performed using a waterless alcohol-based surgical hand scrub with persistent activity following manufacturers recommendations once inside the ante-area; (C)

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29 Hazardous Drugs Handling in Healthcare Settings General Chapter <800> 29

30 Date USP <800>: Timeline History Activity March 28, 2014 General Chapter <800> Posted Online for Public Comment (Published in PF 40(3) May/June 2014) June 12 th, 2014 Open Microphone Web Meeting July 31, 2014 Early August through October 2014 October 13, 2014 December 1, 2014 February 20, 2015 May 31, 2015 Deadline for Submitting Public Comments Hazardous Drug Expert Panel and Subcommittee Reviews ALL comments submitted Notice of Intent to Revise after review of comments submitted Revised GC <800> Posted Online for Public Comment (Published in PF 41(2) March/April 2015) Open Microphone Web Meeting Deadline for Submitting Public Comments February 1, 2016 May 26, 2016 <800> published in the First Supplement to USP 39-NF 34 with a delayed official implementation date of July 1, 2018 Notice of Intent to Revise Errata to correct Section 5.3 revised to indicate that the C-SEC used for sterile and nonsterile compounding must be externally vented. The C-SEC does not need to be vented through HEPA filtration. November 1, 2017 Notice of Intent to Revise Postponement of official implementation date of USP <800> to December 1, 2019, to align with the anticipated official date of USP <797> FAQs

31 USP <800>: Major Differences from <797> Elimination of the exemption for facilities that prepare a low-volume of HDs that permits placement of a BSC or CACI in a non-negative room Allowance of a Containment Segregated Compounding Area (C-SCA), a separate negative pressure room with at least 12 air changes per hour General Chapter <797> will be harmonized with the new proposed chapter BSC or CACI C-SCA Negative 31

32 USP <800>: Why and Existing References Chapter builds on the standards existing in compounding chapters 795 and 797 Adds in the elements of containment of hazardous drugs (HDs) Incorporates principles of medication safety and worker protection from existing references Existing references NIOSH Alert ASHP Guidelines on Handling Hazardous Drugs 32

33 NIOSH Hazardous Drugs History National Institute for Occupational Safety & Health (NIOSH) 2016 Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings Published 2004 Included sample list of major hazardous drugs Renamed: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010 Updates to the list of antineoplastic and other hazardous drugs published 2012, 2014, 2016 (current) HD includes any drug identified by at least one of the following six criteria: Carcinogenicity Teratogenicity or developmental toxicity Reproductive toxicity in humans Organ toxicity at low doses in humans or animals Genotoxicity New drugs that mimic existing HDs in structure or toxicity Privileged and Confidential 33

34 34 USP <800> Chapter Outline 1. Introduction and Scope 2. List of Hazardous Drugs 3. Types of Exposure 4. Responsibilities of Personnel Handling Hazardous Drugs 5. Facilities and Engineering controls 5.1 Receipt 5.2 Storage 5.3 Compounding Nonsterile Compounding Sterile Compounding 5.4 Containment Supplemental Engineering Controls 6. Environmental Quality and Control 7. Personal Protective Equipment 7.1 Gloves 7.2 Gowns 7.3 Head, Hair, Shoe, and Sleeve Covers 7.4 Eye and Face Protection 7.5 Respiratory Protection 7.6 Disposal of Used Personal Protective Equipment 8. Hazard Communication Program 9. Personnel Training 10. Receiving 11. Labeling, Packaging, Transport and Disposal 11.1 Labeling 11.2 Packaging 11.3 Transport 11.4 Disposal 12. Dispensing Final Dosage Forms 13. Compounding 14. Administering 15. Deactivating, Decontaminating, Cleaning, and Disinfecting 15.1 Deactivation 15.2 Decontamination 15.3 Cleaning 15.4 Disinfection 16. Spill Control 17. Documentation and Standard Operating Procedures 18. Medical Surveillance 18.1 Follow-Up Plan Glossary Appendices Appendix 1: Acronyms Appendix 2: Examples off Designs for Hazardous Drug Compounding Areas Appendix 3: Types of Biological Safety Cabinets References

35 1. Introduction and Scope Entities that handle HDs must incorporate the standards in this chapter into their occupational safety plan. Explain how hazardous drugs are defined by USP <800> and NIOSH Understand the three Groups of drugs on the NIOSH Hazardous List Understand how these 3 Groups are categorized Chemotherapy, sterile and non-sterile Hazardous, sterile and non-sterile The entity's health and safety management system must, at a minimum, include: A list of HDs Facility and engineering controls Competent personnel Safe work practices Proper use of appropriate Personal Protective Equipment (PPE) Policies Documentation 35

36 2. List of Hazardous Drugs An entity must maintain a list of HDs, which must include any items on the current NIOSH list that it handles. The list must be reviewed at least every 12 months. The NIOSH list of antineoplastic and other HDs provides the criteria used to identify HDs. These criteria must be used to identify HDs that enter the market after the most recent version of the NIOSH list, or that the entity handles as an investigational drug. If the information available on a drug is deemed insufficient to make an informed decision, consider the drug hazardous until more information is available. 36

37 2. List of Hazardous Drugs Drugs on the NIOSH list that must follow the requirements in this chapter: Any HD API Any antineoplastic requiring HD manipulation Drugs on the NIOSH list that do not have to follow all the containment requirements of this chapter if an assessment of risk is performed and implemented: Final dosage forms of compounded HD preparations and conventionally manufactured HD products that do not require any further manipulation other than counting or repackaging (unless required by the manufacturer e.g. Methotrexate IM Inj.) and dosage forms of other HDs on the NIOSH list. 37

38 3. Types of Exposure Routes of unintentional entry of HDs into the body include dermal and mucosal absorption inhalation injection ingestion This section also lists examples of potential routes of exposure based on activity. (See Table 1 in USP <800>) 38

39 4. Responsibilities of Personnel Handling Hazardous Drugs Each entity must have a designated person who is qualified and trained to be responsible for: developing and implementing procedures overseeing compliance ensuring competency of personnel and ensuring environmental control of the storage and compounding areas. He or she must understand the rationale for risk-prevention policies, risks to themselves and others, risks of noncompliance, and the responsibility to report potentially hazardous situations to management. He or she must also be responsible for the oversight of monitoring the facility and maintaining reports of testing and sampling performed and acting on the results. 39

40 Claiming Your CE Credit Pharmacist: bcyy Pharmacy Technician: WHhW

41 Thank You Lisa D. Ashworth, BS Pharm, RPh, FACA Children s Health System of Texas Compounding Specialist All Campuses Direct: or Mobile: rlisadashworth@gmail.com or lisa.ashworth@childrens.com 41

42 Questions 42